a5532z
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of September 2020
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza recommended for
approval in the EU by CHMP for BRCA-mutated metastatic
castration-resistant prostate cancer
21 September 2020 07:05 BST
Lynparza recommended for approval in the EU by CHMP
for
BRCA-mutated metastatic castration-resistant prostate
cancer
Only PARP inhibitor to improve overall survival vs.
new
hormonal agent treatments in advanced prostate cancer
AstraZeneca and MSD's Lynparza (olaparib) has been recommended for
marketing authorisation in the European Union (EU) for patients
with metastatic castration-resistant prostate cancer (mCRPC)
with breast cancer susceptibility gene 1/2 (BRCA1/2)
mutations, a subpopulation of homologous recombination repair
(HRR) gene mutations.
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency based its positive opinion on a
subgroup analysis of patients with BRCA1/2 mutations from the
PROfound Phase III trial. The primary results from the trial were
published in The
New England Journal of Medicine in May 2020.
Prostate cancer is the second-most common type of cancer in men,
with an estimated 1.3 million new patients diagnosed worldwide in
2018.1 Approximately
12% of men with mCRPC have a BRCA
mutation. 2
José Baselga, Executive Vice President, Oncology R&D,
said: "Patients diagnosed with metastatic castration-resistant
prostate cancer unfortunately have few treatment options and
historically a poor prognosis. This recommendation
for Lynparza brings us closer to making the only PARP
inhibitor to improve overall survival in this setting available to
men in the EU. BRCA testing should now become a critical step
in the diagnosis and determination of treatment for men with
advanced prostate cancer in the EU."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "In the PROfound trial, Lynparza provided a significant clinical benefit to
men with BRCA-mutated metastatic castration-resistant prostate
cancer. If approved, Lynparza could be transformative in the treatment
paradigm, bringing an additional treatment option to certain
prostate cancer patients in the EU."
The CHMP recommendation for Lynparza is for the treatment of adult patients with
mCRPC and BRCA1/2 mutations (germline and/or somatic) who have
progressed following prior therapy that included a new hormonal
agent.
Lynparza was approved in
the US for men with HRR gene-mutated mCRPC
in May
2020 based on the PROfound
Phase III trial. Regulatory reviews are ongoing in other countries
around the world.
AstraZeneca and MSD are exploring additional trials in metastatic
prostate cancer including the ongoing PROpel Phase III trial
testing Lynparza as a 1st-line treatment for patients with
mCRPC in combination with abiraterone versus abiraterone alone.
Data are anticipated in the second half of
2021.
Metastatic castration-resistant prostate cancer
(mCRPC)
Prostate cancer is associated with a significant mortality
rate.1 Development
of prostate cancer is often driven by male sex hormones called
androgens, including testosterone.3 In
patients with mCRPC, their prostate cancer grows and spreads to
other parts of the body despite the use of androgen-deprivation
therapy to block the action of male sex
hormones.3 Approximately
10-20% of men with advanced prostate cancer will develop CRPC
within five years, and at least 84% of these men will have
metastases at the time of CRPC diagnosis.3 Of
men with no metastases at CRPC diagnosis, 33% are likely to develop
metastases within two years.4 Despite
advances in treatment for men with mCRPC, five-year survival is low
and extending survival remains a key treatment
goal.4
BRCA mutations
BRCA1 and BRCA2 are human genes that produce proteins responsible
for repairing damaged DNA and play an important role in maintaining
the genetic stability of cells. When either of these genes is
mutated, or altered, such that its protein product either is not
made or does not function correctly, DNA damage may not be repaired
properly, and cells become unstable. As a result, cells are more
likely to develop additional genetic alterations that can lead to
cancer and confer sensitivity to PARP inhibitors
including Lynparza.5
PROfound
PROfound is a prospective, multicentre, randomized, open-label,
Phase III trial testing the efficacy and safety
of Lynparza versus enzalutamide or abiraterone in
patients with mCRPC who have progressed on prior treatment with NHA
treatments (abiraterone or enzalutamide) and have a qualifying
tumour mutation in BRCA1/2, ATM or one of 12 other genes involved
in the HRR pathway.
The trial was designed to analyse patients with HRR gene mutations
in two cohorts: the primary endpoint was rPFS in those with
mutations in BRCA1/2 or ATM genes and then,
if Lynparza showed clinical benefit, a formal analysis
was performed of the overall trial population of patients with HRR
gene mutations (BRCA1/2, ATM, CDK12 and 11 other HRR gene
mutations). AstraZeneca and MSD announced in August
2019 that the trial met
its primary endpoint of rPFS.
Lynparza
Lynparza (olaparib) is a
first-in-class PARP inhibitor and the first targeted treatment to
block DNA damage response (DDR) in cells/tumours harbouring a
deficiency in HRR, such as mutations in BRCA1 and/or BRCA2.
Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA
single-strand breaks, stalling of replication forks, their collapse
and the generation of DNA double-strand breaks and cancer cell
death. Lynparza is being tested in a range of PARP-dependent
tumour types with defects and dependencies in the DDR
pathway.
Lynparza is currently
approved in a number of countries, including those in the EU, for
the maintenance treatment of platinum-sensitive relapsed ovarian
cancer. It is approved in the US, the EU, Japan, China, and several
other countries as 1st-line maintenance treatment of BRCAm advanced
ovarian cancer following response to platinum-based chemotherapy.
It is also approved in the US as a 1st-line maintenance treatment
with bevacizumab for patients with HRD-positive advanced ovarian
cancer (BRCAm and/or genomic instability). Lynparza is approved in the US, Japan, and a number
of other countries for germline BRCAm, HER2-negative, metastatic
breast cancer, previously treated with chemotherapy; in the EU,
this includes locally advanced breast cancer. It is also approved
in the US and several other countries for the treatment of germline
BRCAm metastatic pancreatic cancer. Lynparza is approved in the US for HRR gene-mutated
mCRPC (BRCAm and other HRR gene mutations). Regulatory reviews are
underway in several countries for ovarian, breast, pancreatic and
prostate cancers.
Lynparza, which is being
jointly developed and commercialised by AstraZeneca and MSD, has
been used to treat over 30,000 patients
worldwide. Lynparza has the broadest and most advanced clinical
trial development programme of any PARP inhibitor, and AstraZeneca
and MSD are working together to understand how it may affect
multiple PARP-dependent tumours as a monotherapy and in combination
across multiple cancer types. Lynparza is the foundation of AstraZeneca's
industry-leading portfolio of potential new medicines targeting DDR
mechanisms in cancer cells.
The AstraZeneca and MSD strategic oncology
collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth,
NJ, US, known as MSD outside the US and Canada, announced a global
strategic oncology collaboration to co-develop and
co-commercialise Lynparza, the world's first PARP inhibitor,
and Koselugo (selumetinib), a mitogen-activated protein
kinase (MEK) inhibitor, for multiple cancer types. Working
together, the companies will develop Lynparza and Koselugo in combination with other potential new
medicines and as monotherapies. Independently, the companies will
develop Lynparza and Koselugo in combination with their respective PD-L1
and PD-1 medicines.
AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a
quickly growing portfolio of new medicines that has the potential to transform
patients' lives and the Company's future. With seven new medicines
launched between 2014 and 2020, and a broad
pipeline of small molecules and biologics in development,
the Company is committed to advance oncology as a key growth driver
for AstraZeneca focused on lung, ovarian, breast and blood
cancers.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development
of personalised combinations, AstraZeneca has the vision to
redefine cancer treatment and, one day, eliminate cancer as a cause
of death.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, Cardiovascular, Renal & Metabolism, and Respiratory
& Immunology. Based in Cambridge, UK, AstraZeneca operates in
over 100 countries and its innovative medicines are used by
millions of patients worldwide. Please
visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Bray et al. (2018). Global cancer statistics 2018: GLOBOCAN
estimates of incidence and mortality worldwide for 36 cancers in
185 countries. CA: A Cancer Journal for
Clinicians, 68(6),
pp.394-424.
2. Abida et al. (2020). Rucaparib in Men With Metastatic
Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2
Gene Alteration. Journal of Clinical
Oncology,
38.
3. Cancer.Net. (2019). Treatment of metastatic castration-resistant
prostate cancer.
www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer [Last
Accessed: September 2020].
4. Kirby, M. (2011). Characterising the castration-resistant
prostate cancer population: a systematic
review. International Journal of
Clinical Practice, 65(11),
pp.1180-1192.
5. Moore, K. (2018). Maintenance Olaparib in Patients with
Newly Diagnosed Advanced Ovarian Cancer. New England Journal of
Medicine, 379(26),
pp.2495-2505.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
21 September
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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